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Article

The Efficacy of Elonide Nasal Corticosteroids in Managing Allergic Rhinitis: A Randomized, Double-Blinded Trial

by
Hardip S. Gendeh
1,2,*,
Aneeza W. Hamizan
1,2,
Salina Husain
1,2,
Azmawati M. Nawi
2,3,
Farah D. Zahedi
1,2,
Nur Fadhilah Megat Ismail
1,2 and
N. Ammal M. Farit
4
1
Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
2
Allergic Unit, Hospital Canselor Tuanku Muhriz, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia
3
Department of Public Health Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
4
Department of Pharmacy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2024, 13(7), 1883; https://doi.org/10.3390/jcm13071883
Submission received: 4 January 2024 / Revised: 5 March 2024 / Accepted: 19 March 2024 / Published: 25 March 2024
(This article belongs to the Section Otolaryngology)
Browse Figures
Versions Notes

Abstract

:
Background: Mometasone furoate nasal spray is efficacious in relieving allergic rhinitis symptoms. The objectives of this study were, firstly, to compare the efficacy of Elonide to Nasonex® and a placebo and secondly, to investigate the side effects of Elonide. Method: This was a prospective, single-centered, double blinded, randomized, placebo-controlled, non-inferiority trial. A total of 163 participants from the Otorhinolaryngology Clinic, Hospital Canselor Tuanku Muhriz (HCTM), were randomized into three treatment groups receiving Elonide (n = 56), Nasonex® (n = 54), and placebo (n = 53) nasal sprays using an online randomizer (Random.org). Treatment was administered for 4 weeks. The primary outcome measure was the Total Nasal Resistance (TNR), and the secondary outcomes were the Visual Analogue Score (VAS) and the Rhinoconjunctivitis Quality of Life Questionnaire (RQOLQ) score. Side effects were recorded. Results: There were significant improvements for all groups from baseline. The Elonide group had the greatest mean difference for all primary and secondary outcomes compared to Nasonex® and the placebo (0.77 ± 2.44 vs. 0.35 ± 1.16, p = 1.00 vs. 0.17 ± 0.82, p = 0.01). Elonide is non-inferior to Nasonex (p = 1.00) and superior to the placebo (p < 0.05). The highest side effects reported were for Nasonex (n = 14, 26%), followed by the placebo (n = 8, 16%) and Elonide (n = 6, 12%); headaches (n = 9, 17%) and sore throat (n = 9, 17%) were the most common. Conclusions: Elonide has similar efficacy to Nasonex® when compared to a placebo in the treatment of AR in adults. Elonide is safe and tolerable, with fewer side effects and no adverse side effects.

1. Introduction

Allergic rhinitis (AR) is an Immunoglobulin (Ig) E-mediated inflammation of the nose upon exposure to previously sensitized allergens [1]. It has a prevalence of almost 40% in the population [2]. Rhinitis symptoms include nasal congestion, runny nose (rhinorrhea), nasal itchiness, and sneezing [3,4]. Severity can be classified into mild and moderate/severe, while its frequency is classified as intermittent and persistent [1]. Allergan avoidance is the key form of management but is impractical as some allergens such as house dust mites and food simply cannot be eradicated or avoided. Long-term pharmacotherapy is required to control symptoms. Newer intranasal corticosteroids such as mometasone furoate (Nasonex®) and fluticasone furoate are effective in managing nasal symptoms as they inhibit the T cell response and interleukins 4 and 5 [5,6]. These second-generation nasal steroids are safe, with low levels of systemic absorption.
Mometasone furoate nasal spray (MFNS), first manufactured as Nasonex® (Merck Sharp & Dohme Corp., Heist-op-den-Berg, Belgium), was granted approval in 1997 for the treatment of allergic rhinitis in children (2–11 years) and adults (12 years and above). Several alternatives to Nasonex® are now available in a generic form since its patent ended in December 2017. Elonide (HOE Pharmaceuticals Sdn. Bhd, Petaling Jaya Malaysia) is a generic nasal spray containing mometasone furoate. Elonide is a more affordable substitute to Nasonex® for the treatment of allergic rhinitis. There have been previous studies comparing generic mometasone furoate to Nasonex®, and the tested generic medication has a similar therapeutic profile and safety compared to Nasonex® [7,8]. A study comparing 72 patients on generic mometasone furoate to 72 patients with its original and 36 receiving a placebo revealed mean changes in the Total Nasal Symptoms Score (TNSS) of −4.30, −4.59, and −1.93 at two weeks, indicating therapeutic equivalence between the generic and original [9].
To our knowledge, there has been no head-to-head study that compares Elonide and Nasonex® in the treatment of allergic rhinitis. Thus, the objective of this study was to compare the efficacy of the MFNSs Elonide and Nasonex® versus a placebo among AR patients. The secondary objective was to assess the side effects of Elonide compared to Nasonex®.

2. Materials and Methods

This study was granted approval by the Research Ethics Committee of UKM (UKM PPI/111/8/JEP-2021-655) and ClinicalTrials.gov Identifier (NCT05912192). All participants provided a written informed consent. This study has fulfilled the CONSORT Checklist. Trial registration ClinicalTrials.gov Identifier: NCT05912192 Funded by Hoe Pharmaceuticals Sdn Bhd, Selangor, Malaysia.

2.1. Study Design

This was a prospective, single-centered, double-blinded, randomized, placebo-controlled trial conducted at the Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia.

2.2. Participants

Eligible participants included adults aged 18 and above with newly diagnosed mild, moderate-to-severe, intermittent, and persistent allergic rhinitis, as defined by AR and its Impact on Asthma (ARIA) [10]. AR was confirmed either via a positive skin prick test or serum IgE toward at least one allergen [4]. A specific IgE serum level of ≥0.35 kU/L was deemed a positive result [11]. Participants were excluded if they had concomitant asthma, other immunodeficiency diseases, pregnancy, another concomitant rhinology disease, were smokers, had a severely deviated nasal septum, any form of malignancy or ciliary dyskinesia such as cystic fibrosis. Use of the following medications were not permitted 30 days before the initial dosing: antihistamines, products that contain nasal corticosteroids and decongestants.

2.3. Intervention

There were three arms involving generic MFNSs (Elonide, 50 mcg/dose, Hoe Pharmaceutical Sdn. Bhd., Petaling Jaya, Malaysia): the original mometasone furoate aqueous nasal spray (Nasonex®, 50 mcg/dose, Merck Sharp, & Dohme Corp. Heist-op-den-Berg, Belgium) and a placebo nasal spray (sodium chloride 0.9%, 50 mcg/dose). The pharmacist packaged nasal sprays using aluminum foil to disguise the bottle labels, performed randomization, and dispensed all three nasal sprays. The pharmacist was responsible for generating a random allocation sequence and labeling the bottles sequentially from number 1 to number 163. Investigators and participants were blinded to the type of spray given. Participants were randomized to one of the three groups of intervention. Randomization was performed using an online randomizer (Random.org).
This study consisted of a pretreatment visit, 30 days of at-home dosing, and a post-treatment visit on day 30 (Figure 1). During the pretreatment visit, patients were screened for eligibility by the presentation of nasal symptoms for AR as per ARIA. Consent was obtained before patients were randomized into one of the treatment arms (Elonide, Nasonex®, or the placebo). They were informed of common side effects of MFNSs and non-efficacious treatment. Primary and secondary outcome tests were performed during the pretreatment and post-treatment visits. Participants were provided one bottle of nasal spray and advised to self-administer one spray per nostril twice daily. Drug administration and symptoms were recorded in a medication diary given. During the 30 days of home administration, compliance was ensured via a follow-up interview and a review of patient diaries. Patients were permitted to have a rescue medication (a loratadine tablet, 10 mg, at maximum once daily) if their symptoms were not tolerable.

2.4. Outcome Measures

The efficacy of the nasal corticosteroids was evaluated using the Visual Analogue Score (VAS, mm), the Rhinoconjunctivitis Quality of Life Questionnaire (RQOLQ), and the Total Nasal Resistance (TNR, Pa/cm3/s). The assessments were carried out during pretreatment and post-treatment visits. The severity of nasal symptoms via VAS ranged from 0 (least severe) to 100 mm (most severe). The RQOLQ with 7 subdomains (sleep symptoms, non-hay symptoms, practical problems, nasal problems, eye problems, and emotional problems) was used to assess quality of life. The nasal response was objectively assessed by measuring the TNR using an NR6 Rhinomanometer medical instrument (GM Instruments Ltd., Irvine, UK). The primary outcome was the TNR measurement value, and the secondary outcomes were the VAS and the RQOLQ score.

2.5. Sample Size

The sample size was calculated using Power and Sample Size Software 3.1 (Dupont & Plummer, 1990). The study looked into a continuous response variable from an independent control and experimental subjects with one control(s) per experimental subject. Based on Sriram et al., 2005, the response within each subject group was normally distributed with a standard deviation (SD) of 0.21 [8]. Suppose the true difference in the experimental and control means is 0.14. Therefore, 36 experimental subjects and 36 control subjects are needed to reject the null hypothesis that the population means of the experimental and control groups are equal with a probability (power) of 0.8. The Type I error probability associated with the test of this null hypothesis is 0.05. Considering a 20% dropout rate, a total of 43 patients were required for each treatment group.

2.6. Statistical Analysis

Efficacy analyses of this study were based on an intention-to-treat population, defined as all randomized participants who received one dose or more of the intervention and completed one efficacy assessment or more during treatment [12]. Safety assessments were based on the safety population, which included all participants who received one dose or more of the study intervention. Baseline demographic variables and adverse effects were summarized by treatment group using descriptive statistics. Changes from the baseline to the mean post treatment for all outcomes were examined using an analysis of variance (ANOVA) with the baseline as a covariate and the treatment as fixed effect. The baseline was defined as the mean symptom score during visit 2 prior to 1 month without any intervention, immediately before the first dose (day 1). A treatment difference of p < 0.05 was considered statistically significant. The onset of action was defined as the first time point after initiation of treatment, when the intervention demonstrated a significant difference in primary outcomes compared with the placebo as long as the significant difference was sustained. the onset was analyzed using an ANOVA, with the baseline as a covariate and the treatment as a fixed effect. All tests were 2-sided, using a significance level of 5%, and all analyses were conducted using SPSS version 22 and higher.

3. Results

3.1. Participants

There were 163 participants who were randomized into three treatment groups: Elonide (n = 56), Nasonex® (n = 54), and a placebo nasal spray (n = 53). Eight participants (4.9%) dropped out, leaving 155 participants who completed the study with satisfactory diary documentation (Figure 2). The reasons for dropout were defaulting on follow-up (n = 6) and a reluctance to continue (n = 2) (Table 1). There were 51 male (31%) and 112 female (69%) subjects, with a mean age of 31.23 (SD 8.29) years (Table 1). There were 157 patients that used a nasal spray solely without antihistamines, Elonide (n = 55), Nasonex® (n = 54), and a placebo (n = 48). Rescue medication use was 0.61% (n = 1) in the Elonide group, 0% (n = 0) in the Nasonex® group, and 3.07% (n = 5) in the placebo group. There was no difference in baseline characteristics between groups (Table 1).

3.2. Efficacy Outcomes

There were improvements in the TNR, VAS, and RQOLQ scores at post treatment within all three groups (Table 2). The mean differences for Elonide were higher than for Nasonex and the placebo for the TNR, the VAS, and the RQOLQ score (Figure 3). Elonide showed a larger improvement in mean values post treatment compared to pretreatment than Nasonex® and placebo. There was a significant difference between Elonide and the placebo (p < 0.05). Elonide showed the same efficacy as Nasonex (p > 0.05) and is superior to the placebo (p < 0.05) (Figure 3).
A post hoc subgroup analyses of the primary end point showed that there was no statistically significant difference between the treatment effect in participants with imputation variables. The imputation variables do not affect the mean difference’s significance. The results were favorable for the actively treated groups (Elonide and Nasonex®) compared to the placebo for all the end points which were statistically significant.

3.3. Safety Outcomes

All treatments showed similar safety profiles with low incidences of side effects (SEs) (Table 3). Side effects related to treatment were headaches, sore throat, cough, nasal dryness, nasal irritation, epistaxis, and imbalance; side effects were reported as mild in most cases. The percentage of participants reporting one or more SEs was larger in the Nasonex® group. The overall SE incidence was 54%, with headaches and sore throat being common. There were no adverse effects.

4. Discussion

Previous studies have found that INC sprays are effective in relieving AR symptoms [13,14,15,16]. Based on ARIA guidelines from 2021, INCs are indicated as first-line treatment for mild (VAS < 5) to severe (VAS > 5) intermittent or persistent AR [10,17,18,19]. The guidelines also suggest a step-up treatment if patients are still symptomatic [10,20,21]. The VAS, RQOLQ score, and TNR showed that Elonide had the same efficacy compared to Nasonex® via both primary and secondary outcomes. This is consistent with previous studies in which a generic MFNS was compared to Nasonex® with similar therapeutic profiles (2 weeks of improvements in the Total Nasal Symptoms and mini-RQLQ scores) and safety, with fewer SEs while relieving AR symptoms [7,8]. This proved that the generic Elonide was constantly as efficacious in treating AR as Nasonex.
Post-treatment assessments were performed at week 4; this is an optimal duration for AR treatment, taking into account that the maximum effect of INCs requires 2 weeks or more [22,23]. Durations beyond 4 weeks have been shown to be non-efficacious for drug testing in perineal allergic rhinitis [22]. The VAS is an appropriate tool for severity evaluations of AR to guide treatment [24,25,26,27,28]. According to ARIA, changes in the VAS greater than 23 mm can be considered of clinical importance and thus reflect responsiveness to treatment [26]. In this study, Elonide had the highest mean difference from baseline (>23 mm), indicating an efficacious response to treatment. However, it was also observed that the mean differences in the VAS from baseline scores were relatively low for this study (Elonide, 23.41 mm; Nasonex®, 17.36 mm; and placebo, 16.96 mm) versus a 29 mm mean difference reported by Demoly et al., 2013 [26]. This could be due to patients’ exposure to allergens (dust mites and food) during the long 4-week period causing a temporary worsening of symptoms prior to the post-treatment visit.
The RQOLQ is a valid, reliable, and reproducible disease-specific global tool on the impact of AR used to evaluate QOL [29,30,31]. Higher scores recorded on the RQOLQ are associated with greater QOL impairment. The minimal-importance clinical difference for the RQOLQ score was 0.5 [29]. The mean difference from baseline for the RQOLQ scores further reduced after 4 weeks (>0.5) for Elonide, Nasonex®, and the placebo to 1.50, 1.32, and 1.29 respectively, with the highest significant mean difference recorded for Elonide. This is consistent with previous studies that have shown improvements in QOL at 2 weeks and 4 weeks of treatment using MFNSs [16,32]. QOL improvements are key as they affect the severity of AR and compliancy. Furthermore, patients must not only depend on INCs for symptomatic improvements; allergen avoidance (where possible) is a mainstay of treatment for AR that should be practiced to ensure better QOL improvements [33].
Rhinomanometry is an objective test used to access the severity of nasal congestion by measuring the difference in the trans-nasal pressure of air flow through the nasal cavity. Its physiological function is to determine the nasal air flow resistance via a pressure gradient over four consecutive breaths. The normal value of nasal resistance in an adult is 0.25 Pa/cm3. This number was taken from previous studies in order to establish a quantitative measure whereby nasal resistance is indicative of nasal obstruction [34,35,36,37]. A lower the flow rate and a higher nasal resistance value indicate a higher degree of nasal obstruction. Therefore, an improvement in rhinomanometry translates into a reduction in nasal congestion [37]. Patients with severe nasal congestion will have a higher TNR, which agrees with current study in which the mean baseline TNR scores for each treatment group were 1.37, 1.17, and 0.81 Pa/cm3/s. The Elonide group showed a higher mean difference from baseline, which indicates a reduction in nasal congestion.
INCs of varying brands have different flow properties known as thixotrophy rates [38]. Nasonex® is an aqueous suspension of a corticosteroid which becomes less viscous when shaken or sprayed and returns to a more viscous state within the nasal passages. The Nasonex® group experienced the highest rate of SEs (26%) compared to Elonide (12%) and the placebo (16%). A good aqueous suspension is one that can cover a larger surface area upon spraying, after which it adheres to the mucosa, resulting in less retrograde flow to the nose and throat discomfort. Elonide should have similar properties to Nasonex® as they share the same content of mometasone furoate [39]. However, Elonide not an aqueous solution and should have a higher viscosity, requiring it to be shaken prior to use. A more viscous solution may adhere to the mucosa and be less likely to flow to the back of the nose. This may be a reason for the fewer SEs of sore throat and cough among the Elonide group. There have yet to be any studies comparing flow properties between both of these INCs.
Mometasone furoate has been shown to be efficacious in reducing nasal symptoms such as nasal blockage, nasal itchiness, sneezing, and rhinorrhea for both seasonal and perineal allergic rhinitis [15,40]. It also has the highest lipophilicity compared to fluticasone propionate, beclomethasone dipropionate, and budesonide, resulting in higher uptake within the nasal mucosa [41]. The side effects of MFNSs from previous studies ranged from 22% to 36% [5,14,42,43] wherein headache is the most common, consistent with the findings of this study. Both the generic and original MFNSs were well tolerated with no adverse drug reactions, further confirming their safety profiles. [14,18,42,43]. This is consistent with previous studies on Nasonex® which showed tolerable adverse events or side effects within 2 to 4 weeks of the study’s duration. There were no adverse drug reactions up to 6 months of outpatient follow-up of the above patients outside the study period [44,45,46].
The placebo had significant improvements for the VAS, the RQLQ score, and the TNR when compared to baseline due to the therapeutic effect of normal saline in relieving AR symptoms [47]. Meta-analyses showed that saline irrigation served as a safe adjunct to AR treatment among children and adults [48,49]. A meta-analysis looked into patient-reported disease severity, wherein normal saline was shown to have a therapeutic effect in relieving symptoms for up to 4 weeks (SMD −1.32, 95% confidence interval (CI) −1.84 to −0.81; 407 participants) in six studies and three months (SMD −1.44, 95% CI −2.39 to −0.48; 167 participants) in five studies [50]. Although normal saline 0.9% was used as a placebo, previous AR-related research studies did not state the type of placebo used [7,8,13,14,15,16]. Five patients within the placebo group required oral antihistamines as rescue medications daily and/or when needed. Since allergen avoidance is a mainstay of treatment, exposure to allergens may also affect the outcomes measured between groups. Therefore, future studies should consider the use of distilled water instead of normal saline as a placebo as the latter has therapeutic benefits.
Multiple imputation (MI) was conducted for missing data at random to preserve the randomized sample size (n = 163) [51]. MI is a popular method of imputing data in randomized clinical trials via predictive mean matching (PMM). It analyses data by imputing missing data for continuous variables and is less sensitive to violations of the normality assumption compared to standard linear regression imputation [52,53]. More than five imputations are performed to avoid a large Monte Carlo error [52]. The number of imputations should be at least greater than the percentage of missing data analyses; the rate of missing data for this study was 4.9%, equivalent to five imputations used [54].
The limitation of this study was a small sample size due to challenges with recruiting newly diagnosed patients without prior INC administration. A cross-over study with a washout period should be considered in the future. Classifying the severity of AR may also allow treatment outcomes among different groups to be analyzed. A short follow-up period is a limitation. Therefore, a longer duration of follow-up within the study period beyond 4 weeks can be considered for better monitoring of adverse events or side effects with time. A lower value of p < 0.05 was not used to indicate significance as results should be interpreted in combination and not depending solely on the p value. Elonide showed greater improvements in mean values for the TNR, the RQLQ score, and the VAS compared to Nasonex® and the placebo [55,56]. The generic version of the MFNS may be a viable alternative to its original counterpart which may be more affordable for developing nations void of national healthcare financing and with patients making high out-of-pocket payments [57].

5. Conclusions

Elonide nasal spray has a similar efficacy and is non-inferior when compared to its original counterpart, Nasonex®, in the treatment of AR in adults. Elonide is safe, tolerable, has fewer side effects with no adverse reactions; it is suitable as a single-modality treatment to improve nasal symptoms.

Author Contributions

Conceptualization, H.S.G., A.W.H., F.D.Z. and S.H.; methodology, H.S.G., A.W.H., F.D.Z. and S.H.; software, H.S.G., A.W.H., F.D.Z. and S.H.; validation, H.S.G. and A.W.H.; formal analysis, H.S.G., A.W.H., A.M.N. and N.F.M.I.; investigation, H.S.G., A.W.H. and N.F.M.I.; resources, H.S.G., A.W.H., N.F.M.I. and N.A.M.F.; data curation, H.S.G., A.W.H., A.M.N. and N.F.M.I.; writing—original draft preparation, H.S.G.; writing—review and editing, H.S.G., A.W.H. and N.F.M.I.; visualization, H.S.G., A.W.H. and N.F.M.I.; supervision, S.H.; project administration, H.S.G.; funding acquisition, H.S.G. All authors have read and agreed to the published version of the manuscript.

Funding

This study received an industrial grant from Hoe Pharmaceuticals Sdn Bhd, Petaling Jaya, Malaysia, a subsidiary of Taisho Pharmaceutical Pte Ltd. (company registration number 45064-A).

Institutional Review Board Statement

Ethical approval was obtained from the Research Ethics Committee of UKM on 17 September 2021 (project code FF-2021-421).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

All additional data and materials are available on request.

Acknowledgments

The authors would like to thank all the patients and physicians who participated in this study. Elonide and the placebo were provided by HOE Pharmaceuticals Sdn. Bhd., Petaling Jaya, Malaysia. This study was funded by HOE Pharmaceuticals Sdn. Bhd, Petaling Jaya, Malaysia. Nasonex was purchased from MS Ally Pharma Sdn Bhd, Kuala Lumpur, Malaysia. The authors thank Hoe Pharmaceutical Sdn Bhd, a subsidiary of Taisho Pharmaceutical Pte Ltd. for financial support and medical writing. All organizations had no role in the study design, data collection, analysis, or decisions and recommendations made by the authors in this manuscript.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Bousquet, J.; Van Cauwenberge, P.; Khaltaev, N.; Aria Workshop Group; World Health Organization. Allergic rhinitis and its impact on asthma. J. Allergy Clin. Immunol. 2001, 108, 147–334. [Google Scholar] [CrossRef]
  2. Bauchau, V.; Durham, S.R. Prevalence and rate of diagnosis of allergic rhinitis in Europe. Eur. Respir. J. 2004, 24, 758–764. [Google Scholar] [CrossRef]
  3. Wise, S.K.; Lin, S.Y.; Toskala, E.; Orlandi, R.R.; Akdis, C.A.; Alt, J.A.; Azar, A.; Baroody, F.M.; Bachert, C.; Canonica, G.W.; et al. International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis. Int. Forum Allergy Rhinol. 2018, 8, 108–352. [Google Scholar] [CrossRef]
  4. Gendeh, B.S.; Murad, S.; Razi, A.M.; Abdullah, N.; Mohamed, A.S.; Kadir, K.A. Skin prick test reactivity to foods in adult Malaysians with rhinitis. Otolaryngol. Head Neck Surg. 2000, 122, 758–762. [Google Scholar] [CrossRef]
  5. Aneeza, W.H.; Husain, S.; Rahman, R.A.; Van Dort, D.; Abdullah, A.; Gendeh, B.S. Efficacy of Mometasone Furoate and Fluticasone Furoate on Persistent Allergic Rhinoconjunctivitis. Allergy Rhinol. 2013, 4, e120–e126. [Google Scholar] [CrossRef]
  6. Corren, J. Intranasal corticosteroids for allergic rhinitis: How do different agents compare? J. Allergy Clin. Immunol. 1999, 104, 144–149. [Google Scholar] [CrossRef]
  7. Gotoh, M.; Sugita, K.; Saito, A.; Honda, T.; Hoashi, K.; Miyazaki, T. A Study of the Therapeutic Equivalence of Generic vs. Mometasone Nasal Spray in Patients with Seasonal Allergic Rhinitis. Nihon Bika Gakkai Kaishi (Jpn. J. Rhinol.) 2018, 57, 7–16. [Google Scholar] [CrossRef]
  8. Vaidyanathan, S.; Barnes, M.; Lipworth, B.J. Comparative safety and efficacy of 2 formulations of fluticasone aqueous nasal spray in persistent allergic rhinitis. Ann. Allergy Asthma Immunol. 2009, 102, 76–83. [Google Scholar] [CrossRef]
  9. Kuribayashi, R.; Kasuga, M.; Kuwana, K.; Yamaguchi, T. First Approval of Generic Mometasone Furoate Nasal Suspension Spray in Japan: Similarities and Differences Between Japan and the USA. Ther. Innov. Regul. Sci. 2022, 57, 173–177. [Google Scholar] [CrossRef]
  10. Klimek, L.; Bachert, C.; Pfaar, O.; Becker, S.; Bieber, T.; Brehler, R.; Buhl, R.; Casper, I.; Chaker, A.; Czech, W.; et al. ARIA guideline 2019: Treatment of allergic rhinitis in the German health system. Allergologie 2019, 3, 22–50. [Google Scholar] [CrossRef]
  11. Heyworth-Smith, D.; Campbell, P. Laboratory Diagnosis of Allergy; QML Pathology Newsletter: Brisbane, Australia, 2017. [Google Scholar]
  12. Gupta, S.K. Intention-to-treat concept: A review. Perspect. Clin. Res. 2011, 2, 109–112. [Google Scholar] [CrossRef]
  13. Buhl, R.; Tanase, A.-M.; Hosoe, M.; Cao, W.; Demin, I.; Bartels, C.; Jauernig, J.; Ziegler, D.; Patalano, F.; Hederer, B.; et al. A randomized, double-blind study to compare the efficacy and safety of two doses of mometasone furoate delivered via Breezhaler® or Twisthaler® in patients with asthma. Pulm. Pharmacol. Ther. 2020, 62, 101919. [Google Scholar] [CrossRef]
  14. Small, C.B.; Hernandez, J.; Reyes, A.; Schenkel, E.; Damiano, A.; Stryszak, P.; Staudinger, H.; Danzig, M. Efficacy and safety of mometasone furoate nasal spray in nasal polyposis. J. Allergy Clin. Immunol. 2005, 116, 1275–1281. [Google Scholar] [CrossRef]
  15. Lange, B.; Lukat, K.-F.; Rettig, K.; Holtappels, G.; Bachert, C. Efficacy, cost-effectiveness, and tolerability of mometasone furoate, levocabastine, and disodium cromoglycate nasal sprays in the treatment of seasonal allergic rhinitis. Ann. Allergy Asthma Immunol. 2005, 95, 272–282. [Google Scholar] [CrossRef]
  16. Mak, K.-K.; Ku, M.-S.; Lu, K.-H.; Sun, H.-L.; Lue, K.-H. Comparison of Mometasone Furoate Monohydrate (Nasonex) and Fluticasone Propionate (Flixonase) Nasal Sprays in the Treatment of Dust Mite-sensitive Children with Perennial Allergic Rhinitis. Pediatr. Neonatol. 2013, 54, 239–245. [Google Scholar] [CrossRef]
  17. Abdul Latiff, A.H.; Husain, S.; Abdullah, B.; Suppiah, P.; Tan, V.; Ing Ping, T.; Woo, K.; Yap, Y.-Y.; Bachert, C.; Schunemann, J.H.; et al. ARIA Care Pathways 2019: Next-Generation Allergic Rhinitis Care and Allergen Immunotherapy in Malaysia. J. Pers. Med. 2023, 13, 835. [Google Scholar] [CrossRef]
  18. Tarmizi, N.E.; Hamizan, A.W.; Ng, C.S.; Gendeh, H.S.; Guan, L.S.; Zahedi, F.D.; Baki, M.M.; Husain, S. The Nasal Endoscopic Features of Postnasal Drip: A Cross Sectional Study. Int. Arch. Otorhinolaryngol. 2023, 28, e95–e100. [Google Scholar] [CrossRef]
  19. Hamizan, A.W.; Rimmer, J.; Alvarado, R.; Sewell, W.A.; Tatersall, J.; Barham, H.P.; Kalish, L.; Harvey, R.J. Turbinate-Specific IgE in Normal and Rhinitic Patients. Am. J. Rhinol. Allergy 2019, 33, 178–183. [Google Scholar] [CrossRef]
  20. Brożek, J.L.; Bousquet, J.; Agache, I.; Agarwal, A.; Bachert, C.; Bosnic-Anticevich, S.; Brignardello-Petersen, R.; Canonica, G.W.; Casale, T.; Chavannes, N.H.; et al. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines—2016 revision. J. Allergy Clin. Immunol. 2017, 140, 950–958. [Google Scholar] [CrossRef]
  21. Dykewicz, M.S.; Wallace, D.V.; Baroody, F.; Bernstein, J.; Craig, T.; Finegold, I.; Huang, F.; Larenas-Linnemann, D.; Meltzer, E.; Steven, G.; et al. Treatment of seasonal allergic rhinitis: An evidence-based focused 2017 guideline update. Ann. Allergy Asthma Immunol. 2017, 119, 489–511. [Google Scholar] [CrossRef]
  22. Krouse, J.H.; Roland, P.S.; Marple, B.F.; Wall, G.M.; Hannley, M.; Golla, S.; Hunsaker, D. Optimal Duration of Allergic Rhinitis Clinical Trials. Otolaryngol. Neck Surg. 2005, 133, 467–487, discussion 488. [Google Scholar] [CrossRef] [PubMed]
  23. Scadding, G.K.; Durham, S.R.; Mirakian, R.; Jones, N.S.; Leech, S.C.; Farooque, S.; Ryan, D.; Walker, S.M.; Clark, A.T.; Dixon, T.A.; et al. British Society for Allergy and Clinical Immunology. BSACI guidelines for the management of allergic and non-allergic rhinitis. Clin. Exp. Allergy 2008, 38, 19–42. [Google Scholar] [CrossRef]
  24. Klimek, L.; Bergmann, K.C.; Biedermann, T.; Bousquet, J.; Hellings, P.; Jung, K.; Merk, H.; Olze, H.; Schlenter, W.; Stock, P.; et al. Visual analogue scales (VAS): Measuring instruments for the documentation of symptoms and therapy monitoring in cases of allergic rhinitis in everyday health care: Position Paper of the German Society of Allergology (AeDA) and the German Society of Allergy and Clinical Immunology (DGAKI), ENT Section, in collaboration with the working group on Clinical Immunology, Allergology and Environmental Medicine of the German Society of Otorhinolaryngology, Head and Neck Surgery (DGHNOKHC). Allergo J. Int. 2017, 26, 16–24. [Google Scholar]
  25. Larenas-Linnemann, D.; Dinger, H.; Shah-Hosseini, K.; Michels, A.; Mösges, R.; Mexican Study Group on Allergic Rhinitis and SPT Sensitivity. Over Diagnosis of Persistent Allergic Rhinitis in Perennial Allergic Rhinitis Patients: A Nationwide Study in Mexico. Am. J. Rhinol. Allergy 2013, 27, 495–501. [Google Scholar] [CrossRef]
  26. Demoly, P.; Bousquet, P.J.; Mesbah, K.; Bousquet, J.; Devillier, P. Visual analogue scale in patients treated for allergic rhinitis: An observational prospective study in primary care. Clin. Exp. Allergy 2013, 43, 881–888. [Google Scholar] [CrossRef]
  27. Bousquet, J.; Bachert, C.; Canonica, G.W.; Mullol, J.; Van Cauwenberge, P.; Jensen, C.B.; Fokkens, W.J.; Ring, J.; Keith, P.; Lorber, R.; et al. Efficacy of desloratadine in intermittent allergic rhinitis: A GA2LEN study. Allergy 2009, 64, 1516–1523. [Google Scholar] [CrossRef] [PubMed]
  28. Bousquet, J.; Bachert, C.; Canonica, G.W.; Mullol, J.; Van Cauwenberge, P.; Jensen, C.B.; Fokkens, W.J.; Ring, J.; Keith, P.; Gopalan, G.; et al. Efficacy of desloratadine in persistent allergic rhinitis—A GA2LEN study. Int. Arch. Allergy Immunol. 2010, 153, 395–402. [Google Scholar] [CrossRef]
  29. Juniper, E.F.; Guyatt, G.H.; Griffith, L.E.; Ferrie, P.J. Interpretation of rhinoconjunctivitis quality of life questionnaire data. J. Allergy Clin. Immunol. 1996, 98, 843–845. [Google Scholar] [CrossRef]
  30. Juniper, E.F.; Guyatt, G.H. Development and testing of a new measure of health status for clinical trials in rhinoconjunctivitis. Clin. Exp. Allergy 1991, 21, 77–83. [Google Scholar] [CrossRef]
  31. Juniper, E.F.; Thompson, A.K.; Ferrie, P.J.; Roberts, J.N. Validation of the standardized version of the Rhinoconjunctivitis Quality of Life Questionnaire. J Allergy Clin Immunol. 1999, 104, 364–369. [Google Scholar] [CrossRef]
  32. Yamada, T.; Yamamoto, H.; Kubo, S.; Sakashita, M.; Tokunaga, T.; Susuki, D.; Narita, N.; Ogi, K.; Kanno, M.; Yamashita, S.; et al. Efficacy of mometasone furoate nasal spray for nasal symptoms, quality of life, rhinitis-disturbed sleep, and nasal nitric oxide in patients with perennial allergic rhinitis. Allergy Asthma Proc. 2012, 33, e9–e16. [Google Scholar] [CrossRef]
  33. Marple, B.F.; Fornadley, J.A.; Patel, A.A.; Fineman, S.M.; Fromer, L.; Krouse, J.H.; Lanier, B.Q.; Penna, P.; American Academy of Otolaryngic Allergy Working Group on Allergic Rhinitis. Keys to successful management of patients with allergic rhinitis: Focus on patient confidence, compliance, and satisfaction. Otolaryngol. Neck Surg. 2007, 136, S107–S124. [Google Scholar] [CrossRef]
  34. Juliá, J.C.; Burchés, M.E.; Martorell, A. Active anterior rhinomanometry in paediatrics. Normality criteria. Allergol. Et Immunopathol. 2011, 39, 342–346. [Google Scholar] [CrossRef]
  35. Carney, A.; Bateman, N.; Jones, N. Reliable and reproducible anterior active rhinomanometry for the assessment of unilateral nasal resistance. Clin. Otolaryngol. 2000, 25, 499–503. [Google Scholar] [CrossRef]
  36. Takeuchi, H.; Jawad, M.; Eccles, R. Changes in unilateral nasal airflow in patients with seasonal allergic rhinitis measured in and out of season. Auris Nasus Larynx 2000, 27, 141–145. [Google Scholar] [CrossRef]
  37. Kobayashi, R.; Miyazaki, S.; Karaki, M.; Kobayashi, E.; Karaki, R.; Akiyama, K.; Matsubara, A.; Mori, N. Measurement of nasal resistance by rhinomanometry in 892 Japanese elementary school children. Auris Nasus Larynx 2011, 38, 73–76. [Google Scholar] [CrossRef]
  38. Sharpe, S.A.; Sandweiss, V.; Tuazon, J.; Giordano, M.; Witchey-Lakshmanan, L.; Hart, J.; Sequeira, J. Comparison of the Flow Properties of Aqueous Suspension Corticosteroid Nasal Sprays Under Differing Sampling Conditions. Drug Dev. Ind. Pharm. 2003, 29, 1005–1012. [Google Scholar] [CrossRef]
  39. Elonide (Mometasone Furoate) Nasal Spray, 50 mcg Full Prescribing Info. Available online: https://www.mims.com/malaysia/drug/info/elonide?type=full (accessed on 3 January 2024).
  40. Mandl, M.; Nolop, K.; Lutsky, B. Comparison of Once Daily Mometasone Furoate (Nasonex) and Fluticasone Propionate Aqueous Nasal Sprays for the Treatment of Perennial Rhinitis. Ann. Allergy Asthma Immunol. 1997, 79, 370–378. [Google Scholar] [CrossRef]
  41. Rollema, C.; van Roon, E.N.; van Boven, J.F.M.; Hagedoorn, P.; Klemmeier, T.; Kocks, J.H.; Metting, E.I.; Elberink, H.N.G.O.; Peters, T.T.A.; Giorgi, M.R.M.S.; et al. Pharmacology, particle deposition and drug administration techniques of intranasal corticosteroids for treating allergic rhinitis. Clin. Exp. Allergy 2022, 52, 1247–1263. [Google Scholar] [CrossRef]
  42. Penagos, M.; Compalati, E.; Tarantini, F.; Baena-Cagnani, C.E.; Passalacqua, G.; Canonica, G.W. Efficacy of mometasone furoate nasal spray in the treatment of allergic rhinitis. Meta-analysis of randomized, double-blind, placebo-controlled, clinical trials. Allergy 2008, 63, 1280–1291. [Google Scholar] [CrossRef]
  43. Meltzer, E.O.; Bachert, C.; Staudinger, H. Treating acute rhinosinusitis: Comparing efficacy and safety of mometasone furoate nasal spray, amoxicillin, and placebo. J. Allergy Clin. Immunol. 2005, 116, 1289–1295. [Google Scholar] [CrossRef] [PubMed]
  44. Gawchik, S.; Goldstein, S.; Prenner, B.; John, A. Relief of cough and nasal symptoms associated with allergic rhinitis by mometasone furoate nasal spray. Ann. Allergy Asthma Immunol. 2003, 90, 416–421. [Google Scholar] [CrossRef] [PubMed]
  45. Berkowitz, R.B.; Bernstein, D.I.; LaForce, C.; Pedinoff, A.J.; Rooklin, A.R.; Damaraju, C.R.; Mesarina-Wicki, B.; Nolop, K.B. Onset of action of mometasone furoate nasal spray (NASONEX) in seasonal allergic rhinitis. Allergy 1999, 54, 64–69. [Google Scholar] [CrossRef]
  46. Bronsky, E.A.; Aaronson, D.W.; Berkowitz, R.B.; Chervinsky, P.; Graft, D.; Kaiser, H.B.; Moss, B.; Nathan, R.A.; Pearlman, D.S.; Ratner, P.H.; et al. Dose ranging study of mometasone furoate (Nasonex) in seasonal allergic rhinitis. Ann. Allergy Asthma Immunol. 1997, 79, 51–56. [Google Scholar] [CrossRef]
  47. Carvalho, V.; Olej, B.; de Moraes, J.R.; Boechat, J.L. Mometasone furoate is not superior to saline for chronic rhinitis in the elderly. World Allergy Organ. J. 2019, 12, 100064. [Google Scholar] [CrossRef]
  48. Madison, S.; Brown, E.A.; Franklin, R.; A Wickersham, E.; McCarthy, L.H. Clinical Question: Nasal saline or intranasal corticosteroids to treat allergic rhinitis in children. J. Okla State Med. Assoc. 2016, 109, 152–153. [Google Scholar]
  49. Wang, Y.; Jin, L.; Liu, S.-X.; Fan, K.; Qin, M.-L.; Yu, S.-Q. Role of nasal saline irrigation in the treatment of allergic rhinitis in children and adults: A systematic analysis. Allergol. et Immunopathol. 2020, 48, 360–367. [Google Scholar] [CrossRef]
  50. Head, K.; Snidvongs, K.; Glew, S.; Scadding, G.; Schilder, A.G.; Philpott, C.; Hopkins, C. Saline irrigation for allergic rhinitis. Cochrane Database Syst. Rev. 2018, 6, CD012597. [Google Scholar] [CrossRef]
  51. Zhu, X. Comparison of Four Methods for Handing Missing Data in Longitudinal Data Analysis through a Simulation Study. Open J. Stat. 2014, 1, 933–944. [Google Scholar] [CrossRef]
  52. Rezvan, P.H.; Lee, K.J.; A Simpson, J. The rise of multiple imputation: A review of the reporting and implementation of the method in medical research. BMC Med. Res. Methodol. 2015, 15, 30. [Google Scholar] [CrossRef]
  53. Austin, P.C.; White, I.R.; Lee, D.S.; van Buuren, S. Missing Data in Clinical Research: A Tutorial on Multiple Imputation. Can. J. Cardiol. 2020, 37, 1322–1331. [Google Scholar] [CrossRef] [PubMed]
  54. White, I.R.; Royston, P.; Wood, A.M. Multiple imputation using chained equations: Issues and guidance for practice. Stat. Med. 2010, 30, 377–399. [Google Scholar] [CrossRef] [PubMed]
  55. Di Leo, G.; Sardanelli, F. Statistical significance: P value, 0.05 threshold, and applications to radiomics—Reasons for a conservative approach. Eur. Radiol. Exp. 2020, 4, 18. [Google Scholar] [CrossRef] [PubMed]
  56. Guideline on The Choice of the Non-Inferiority Margin. Committee for Medicinal Products for Human Use. European Medicines Agency. 2005. Available online: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-choice-non-inferiority-margin_en.pdf (accessed on 3 January 2024).
  57. Ministry of Health Malaysia. Malaysia National Health Accounts. Health Expenditure Report 1997–2019. 2021. Available online: https://www.moh.gov.my/moh/resources/Penerbitan/Penerbitan%20Utama/MNHA/MNHA_Health_Expenditure_Report_1997-2019_02092021.pdf (accessed on 3 January 2024).
Jcm 13 01883 g001
Figure 1. Study flow chart. During the at-home period, for 30 days, patients self-administered the drug studied with doses approximately 12 h apart. The patients’ diaries were used to record symptom assessments and compliancy. IC, inclusion criteria; EC, exclusion criteria; TNR, Total Nasal Resistance; VAS, Visual Analogue Score; RQOLQ, Rhinoconjunctivitis Quality of Life Questionnaire.
Figure 1. Study flow chart. During the at-home period, for 30 days, patients self-administered the drug studied with doses approximately 12 h apart. The patients’ diaries were used to record symptom assessments and compliancy. IC, inclusion criteria; EC, exclusion criteria; TNR, Total Nasal Resistance; VAS, Visual Analogue Score; RQOLQ, Rhinoconjunctivitis Quality of Life Questionnaire.
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Figure 2. Flow of patients in the study design.
Figure 2. Flow of patients in the study design.
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Figure 3. Data distribution with mean plots (♦) for (a) TNR (b) VAS, and (c) RQOLQ score with p values. * indicates significant p value (p < 0.05).
Figure 3. Data distribution with mean plots (♦) for (a) TNR (b) VAS, and (c) RQOLQ score with p values. * indicates significant p value (p < 0.05).
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Table 1. Demographic and baseline characteristics (safety population).
Table 1. Demographic and baseline characteristics (safety population).
CharacteristicsTotalElonideNasonexPlacebop Value
Subjects randomized to treatment, No. (%)163 (100)56 (34)54 (33)53 (33)-
Age, mean (SD), (y)31.23 (8.29)32.16 (8.61)31.57 (8.41)29.91 (7.78)0.25
Gender, No. (%)
Male51 (31.29)19 (33.93)16 (29.63)16 (30.19)0.87
Female112 (68.71)37 (66.07)38 (70.37)37 (69.81)
Intent to treat (ITT)163565453-
Subjects completed treatment155535250-
Subjects discontinued treatment, No. (%)8 (4.9)3 (1.84)2 (1.23)3 (1.84)-
Reason for discontinuation:
Lost to follow-up6222-
Did not wish to continue2101-
Medication(s):
Nasal spray only, No. (%)157 (96.32)55 (33.74)54 (33.13)48 (29.45)-
Nasal spray + antihistamine, No. (%)6 (3.68)1 (0.61)0 (0)5 (3.07)-
VAS (mm), mean (SD) ᵃ56.32 (19.74)57.09 (17.14)54.61 (20.71)57.25 (21.38)0.71
RQOLQ, mean (SD) ᵃ2.98 (1.30)2.87 (1.17)2.91 (1.38)3.15 (1.36)0.49
TNR (Pa/cm3/s), mean (SD) ᵃ1.12 (1.62)1.37 (2.55)1.17 (1.48)0.81 (0.83)0.26
Abbreviations: VAS, Visual Analogue Score; RQOLQ, Rhinoconjunctivitis Quality of Life Questionnaire; TNR, Total Nasal Resistance. Nasal sprays were dosed as one puff twice daily; ᵃ intent-to-treat population.
Table 2. Mean (SD) values for pretreatment and post-treatment (intent-to-treat population) within respective groups.
Table 2. Mean (SD) values for pretreatment and post-treatment (intent-to-treat population) within respective groups.
Treatment GroupOutcome MeasuresPretreatmentPost-Treatmentp Value
ElonideTNR (Pa/cm3/s)1.37 (2.55)0.56 (0.35)<0.01
VAS (mm)57.09 (17.14)33.90 (17.80)<0.01
RQOLQ2.87 (1.17)1.39 (0.95)<0.01
Nasonex®TNR (Pa/cm3/s)1.17 (1.48)0.77 (0.60)<0.01
VAS (mm)54.61 (20.71)37.04 (21.73)<0.01
RQOLQ2.91 (1.38)1.59 (1.22)<0.01
PlaceboTNR (Pa/cm3/s)0.81 (0.83)0.64 (0.40)<0.01
VAS (mm)57.25 (21.38)40.51 (21.48)<0.01
RQOLQ3.15 (1.36)1.88 (1.39)<0.01
Abbreviations: VAS, Visual Analogue Score; RQOLQ, Rhinoconjunctivitis Quality of Life Questionnaire; TNR, Total Nasal Resistance. Nasal sprays were dosed as one puff twice daily.
Table 3. Number of subjects (%) with side effects considered to be related to treatment.
Table 3. Number of subjects (%) with side effects considered to be related to treatment.
Treatment Group
Side EffectsElonide (n = 56)Nasonex® (n = 54)Placebo (n = 53)Total
Headaches2 (4%)4 (7%)3 (6%)9 (17%)
Sore throat2 (4%)4 (7%)3 (6%)9 (17%)
Cough1 (2%)2 (4%)1 (2%)4 (8%)
Nasal dryness1 (2%)1 (2%)0 (0%)2 (4%)
Nasal irritation0 (0%)1 (2%)1 (2%)2 (4%)
Epistaxis0 (0%)1 (2%)0 (0%)1 (2%)
Imbalance0 (0%)1 (2%)0 (0%)1 (2%)
Total6 (12%)14 (26%)8 (16%)28 (54%)
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MDPI and ACS Style

Gendeh, H.S.; Hamizan, A.W.; Husain, S.; Nawi, A.M.; Zahedi, F.D.; Megat Ismail, N.F.; M. Farit, N.A. The Efficacy of Elonide Nasal Corticosteroids in Managing Allergic Rhinitis: A Randomized, Double-Blinded Trial. J. Clin. Med. 2024, 13, 1883. https://doi.org/10.3390/jcm13071883

AMA Style

Gendeh HS, Hamizan AW, Husain S, Nawi AM, Zahedi FD, Megat Ismail NF, M. Farit NA. The Efficacy of Elonide Nasal Corticosteroids in Managing Allergic Rhinitis: A Randomized, Double-Blinded Trial. Journal of Clinical Medicine. 2024; 13(7):1883. https://doi.org/10.3390/jcm13071883

Chicago/Turabian Style

Gendeh, Hardip S., Aneeza W. Hamizan, Salina Husain, Azmawati M. Nawi, Farah D. Zahedi, Nur Fadhilah Megat Ismail, and N. Ammal M. Farit. 2024. "The Efficacy of Elonide Nasal Corticosteroids in Managing Allergic Rhinitis: A Randomized, Double-Blinded Trial" Journal of Clinical Medicine 13, no. 7: 1883. https://doi.org/10.3390/jcm13071883

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